13 research outputs found
Hierarchical Self-Assembly of a Copolymer-Stabilized Coacervate Protocell
Complex
coacervate microdroplets are finding increased utility
in synthetic cell applications due to their cytomimetic properties.
However, their intrinsic membrane-free nature results in instability
that limits their application in protocell research. Herein, we present
the development of a new protocell model through the spontaneous interfacial
self-assembly of copolymer molecules on biopolymer coacervate microdroplets.
This hierarchical protocell model not only incorporates the favorable
properties of coacervates (such as spontaneous assembly and macromolecular
condensation) but also assimilates the essential features of a semipermeable
copolymeric membrane (such as discretization and stabilization). This
was accomplished by engineering an asymmetric, biodegradable triblock
copolymer molecule comprising hydrophilic, hydrophobic, and polyanionic
components capable of direct coacervate membranization via electrostatic
surface anchoring and chain self-association. The resulting hierarchical
protocell demonstrated striking integrity as a result of membrane
formation, successfully stabilizing enzymatic cargo against coalescence
and fusion in discrete protocellular populations. The semipermeable
nature of the copolymeric membrane enabled the incorporation of a
simple enzymatic cascade, demonstrating chemical communication between
discrete populations of neighboring protocells. In this way, we pave
the way for the development of new synthetic cell constructs
RPE cell size and relative abundance of binucleate RPE cells across the mouse and human retina.
<p>(A-C) Confocal images of a flatmount of a BALB/C mouse RPE, showing cells at retinal eccentricities of 0° (A), 40° (B), and 75° (C). Scale bar = 50 μm. (D) Graph of RPE cell cross-sectional area in relation to eccentricity in the mouse and human retinas. RPE cell size was significantly different between eccentricities in both mouse strains (<i>P</i> < 0.0001; Tukey’s test). (E) Graph of RPE cell density in relation to eccentricity in the mouse retinas, illustrating the proportion of binucleate cells, which was different between eccentricities in both mouse strains (<i>P</i> < 0.0001; Tukey’s test). Error bars in D and E indicate SEM. The human data are from Ts’o and Friedman [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125631#pone.0125631.ref039" target="_blank">39</a>].</p
Bruch’s membrane and elastin layer thickness.
<p>(A) EM micrograph of Bruch’s membrane in a BALB/C mouse retina at an eccentricity of 40°. BM, Basement membrane; OC, Outer collagenous layer; EL, Elastin layer; ICL, Inner collagenous layer. Scale bar = 1 μm. (B, D) Graphs of the thickness of the entire Bruch’s membrane in relation to eccentricity in mouse and human retinas. (C, E) Graphs of the thickness of the elastin layer of Bruch’s membrane in relation to eccentricity in mouse and human retinas. The thickness of Bruch's membrane as well as the elastin layer varied very significantly between retinal eccentricities in both mouse strains (<i>P</i> < 0.0001; Tukey’s test). Error bars indicate SEM. The human data, shown in D and E, are from Newsome et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125631#pone.0125631.ref018" target="_blank">18</a>].</p
Mean rod and cone densities in different regions of the human macula and the central mouse retina.
<p><sup>(1)</sup> Human data from [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125631#pone.0125631.ref038" target="_blank">38</a>] temporal from fovea</p><p><sup>(2)</sup> Mouse data from C57BL/6J; dorsal from optical axis</p><p>Mean rod and cone densities in different regions of the human macula and the central mouse retina.</p
The number of photoreceptors per RPE cell in mouse and human eyes.
<p>This cell ratio differed at different eccentricities in both mouse strains (<i>P</i> < 0.0001; Tukey’s test). The human data are from Osterberg [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125631#pone.0125631.ref038" target="_blank">38</a>] and Ts’o and Friedman [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125631#pone.0125631.ref039" target="_blank">39</a>].</p
Comparison of photoreceptor distribution in mouse and human retinas.
<p>(A) Graph showing the photoreceptor density per mm<sup>2</sup> in mouse and human. Data from the visual angles of 0°, 20° and 40° were collected at distances of 0, 0.6 and 1.2 mm, respectively, from the center of the mouse retina, along the dorso-ventral axis (shown left to right; ON indicates the location of the optic nerve head, which is just ventral from the center). Data from the visual angles of 75° and 82° were collected from regions centered at distances of 250 and 50 μm from the ora serrata, which approximated to 2.3 and 2.5 mm from the center. Error bars indicate SEM. Inset shows a low power micrograph of a dorso-ventral section passing through the optic nerve head and the center of the retina (0°); scale bar = 0.3 mm. The human data are from temporal to nasal, as reported by Osterberg [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125631#pone.0125631.ref038" target="_blank">38</a>]. Visual angles of 20°, 40°, 60° and 70° correspond to distances of 6, 12, 18 and 20 mm from the fovea. (B-J) Representative light microscopic images of the regions sampled along the dorsoventral axis of the mouse retinas. Examples from both the BALB/C and C57BL/6J strains are included. (B) 82° dorsal, (C) 75° dorsal, (D) 40° dorsal, (E) 20° dorsal, (F) center, (G) 20° ventral, (H) 40° ventral, (I) 75° ventral, (J) 82° ventral. Scale bar = 25 μm.</p
Erythrocyte Membrane Modified Janus Polymeric Motors for Thrombus Therapy
We report the construction
of erythrocyte membrane-cloaked Janus
polymeric motors (EM-JPMs) which are propelled by near-infrared (NIR)
laser irradiation and are successfully applied in thrombus ablation.
Chitosan (a natural polysaccharide with positive charge, CHI) and
heparin (glycosaminoglycan with negative charge, Hep) were selected
as wall materials to construct biodegradable and biocompatible capsules
through the layer-by-layer self-assembly technique. By partially coating
the capsule with a gold (Au) layer through sputter coating, a NIR-responsive
Janus structure was obtained. Due to the asymmetric distribution of
Au, a local thermal gradient was generated upon NIR irradiation, resulting
in the movement of the JPMs through the self-thermophoresis effect.
The reversible “on/off” motion of the JPMs and their
motile behavior were easily tuned by the incident NIR laser intensity.
After biointerfacing the Janus capsules with an erythrocyte membrane,
the EM-JPMs displayed red blood cell related properties, which enabled
them to move efficiently in relevant biological environments (cell
culture, serum, and blood). Furthermore, this therapeutic platform
exhibited excellent performance in ablation of thrombus through photothermal
therapy. As man-made micromotors, these biohybrid EM-JPMs hold great
promise of navigating <i>in vivo</i> for active delivery
while overcoming the drawbacks of existing synthetic therapeutic platforms.
We expect that this biohybrid motor has considerable potential to
be widely used in the biomedical field
Morphology Under Control: Engineering Biodegradable Stomatocytes
Biodegradable nanoarchitectures,
with well-defined morphological
features, are of great importance for nanomedical research; however,
understanding (and thereby engineering) their formation is a substantial
challenge. Herein, we uncover the supramolecular potential of PEG–PDLLA
copolymers by exploring the physicochemical determinants that result
in the transformation of spherical polymersomes into stomatocytes.
To this end, we have engineered blended polymersomes (comprising copolymers
with varying lengths of PEG), which undergo solvent-dependent reorganization
inducing negative spontaneous membrane curvature. Under conditions
of anisotropic solvent composition across the PDLLA membrane, facilitated
by the dialysis methodology, we demonstrate osmotically induced stomatocyte
formation as a consequence of changes in PEG solvation, inducing negative
spontaneous membrane curvature. Controlled formation of unprecedented,
biodegradable stomatocytes represents the unification of supramolecular
engineering with the theoretical understanding of shape transformation
phenomena
Erythrocyte Membrane Modified Janus Polymeric Motors for Thrombus Therapy
We report the construction
of erythrocyte membrane-cloaked Janus
polymeric motors (EM-JPMs) which are propelled by near-infrared (NIR)
laser irradiation and are successfully applied in thrombus ablation.
Chitosan (a natural polysaccharide with positive charge, CHI) and
heparin (glycosaminoglycan with negative charge, Hep) were selected
as wall materials to construct biodegradable and biocompatible capsules
through the layer-by-layer self-assembly technique. By partially coating
the capsule with a gold (Au) layer through sputter coating, a NIR-responsive
Janus structure was obtained. Due to the asymmetric distribution of
Au, a local thermal gradient was generated upon NIR irradiation, resulting
in the movement of the JPMs through the self-thermophoresis effect.
The reversible “on/off” motion of the JPMs and their
motile behavior were easily tuned by the incident NIR laser intensity.
After biointerfacing the Janus capsules with an erythrocyte membrane,
the EM-JPMs displayed red blood cell related properties, which enabled
them to move efficiently in relevant biological environments (cell
culture, serum, and blood). Furthermore, this therapeutic platform
exhibited excellent performance in ablation of thrombus through photothermal
therapy. As man-made micromotors, these biohybrid EM-JPMs hold great
promise of navigating <i>in vivo</i> for active delivery
while overcoming the drawbacks of existing synthetic therapeutic platforms.
We expect that this biohybrid motor has considerable potential to
be widely used in the biomedical field
Erythrocyte Membrane Modified Janus Polymeric Motors for Thrombus Therapy
We report the construction
of erythrocyte membrane-cloaked Janus
polymeric motors (EM-JPMs) which are propelled by near-infrared (NIR)
laser irradiation and are successfully applied in thrombus ablation.
Chitosan (a natural polysaccharide with positive charge, CHI) and
heparin (glycosaminoglycan with negative charge, Hep) were selected
as wall materials to construct biodegradable and biocompatible capsules
through the layer-by-layer self-assembly technique. By partially coating
the capsule with a gold (Au) layer through sputter coating, a NIR-responsive
Janus structure was obtained. Due to the asymmetric distribution of
Au, a local thermal gradient was generated upon NIR irradiation, resulting
in the movement of the JPMs through the self-thermophoresis effect.
The reversible “on/off” motion of the JPMs and their
motile behavior were easily tuned by the incident NIR laser intensity.
After biointerfacing the Janus capsules with an erythrocyte membrane,
the EM-JPMs displayed red blood cell related properties, which enabled
them to move efficiently in relevant biological environments (cell
culture, serum, and blood). Furthermore, this therapeutic platform
exhibited excellent performance in ablation of thrombus through photothermal
therapy. As man-made micromotors, these biohybrid EM-JPMs hold great
promise of navigating <i>in vivo</i> for active delivery
while overcoming the drawbacks of existing synthetic therapeutic platforms.
We expect that this biohybrid motor has considerable potential to
be widely used in the biomedical field